caa a22 4500 445331208 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-010-9411-0 doi (NATIONALLICENCE)springer-10.1007/s10689-010-9411-0 Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma [Elektronische Daten] [Ingrid Slade, Anne Murray, Sandra Hanks, Ajith Kumar, Lisa Walker, Darren Hargrave, Jenny Douglas, Charles Stiller, Louise Izatt, Nazneen Rahman] PTCH1 and SUFU are both regulators of the sonic hedgehog signalling pathway. Germline inactivating mutations in both genes are associated with multisystem phenotypes including medulloblastoma. Somatic inactivating mutations in PTCH1 and SUFU each occur in approximately 10% of medulloblastomas. Recently, SUFU mutations were reported in familial medulloblastoma pedigrees without additional phenotypic features. We sought to further investigate the contribution of germline PTCH1 and SUFU mutations to familial and sporadic medulloblastoma. We performed full-gene mutational analysis of both PTCH1 and SUFU in three familial medulloblastoma pedigrees and 83 individuals with sporadic non-familial medulloblastoma. We identified no mutations in PTCH1 or SUFU in the three familial medulloblastoma pedigrees. We identified no PTCH1 mutations and two SUFU mutations that cause premature protein truncating in the series of sporadic non-familial medulloblastomas. The SUFU mutations were identified in two of the 16 individuals with desmoplastic medulloblastomas. These data indicate that familial medulloblastoma is a genetically heterogeneous disorder with at least one further susceptibility gene to be discovered. Furthermore, although both PTCH1 and SUFU play a key role in the sonic hedgehog signalling pathway, PTCH1 does not make an appreciable contribution to non-familial sporadic medulloblastoma, whereas inactivating germline mutations of SUFU cause ~2-3% of sporadic medulloblastomas and>10% of desmoplastic medulloblastomas. Springer Science+Business Media B.V., 2010 Familial medulloblastoma nationallicence Medulloblastoma nationallicence PTCH1 nationallicence SUFU nationallicence Tumor predisposition nationallicence MBEN : Medulloblastoma with extensive nodularity nationallicence NBCCS : Nevoid basal cell carcinoma syndrome nationallicence CCLG : Children's cancer and leukaemia group nationallicence PCR : Polymerase chain reaction nationallicence Slade Ingrid Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut Murray Anne Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut Hanks Sandra Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut Kumar Ajith Department of Clinical Genetics, Great Ormond Street Hospital, London, UK aut Walker Lisa Department of Clinical Genetics, Churchill Hospital, Old Road, Headington, Oxford, UK aut Hargrave Darren Section of Paediatrics, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK aut Douglas Jenny Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut Stiller Charles Childhood Cancer Research Group, Department of Paediatrics, University of Oxford, Oxford, UK aut Izatt Louise Department of Clinical Genetics, Guy's and St Thomas' Hospital, London, UK aut Rahman Nazneen Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut Familial Cancer Springer Netherlands 10/2(2011-06-01), 337-342 1389-9600 10:2<337 2011 10 10689 https://doi.org/10.1007/s10689-010-9411-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-010-9411-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Slade Ingrid Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut NATIONALLICENCE 700 1- Murray Anne Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut NATIONALLICENCE 700 1- Hanks Sandra Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut NATIONALLICENCE 700 1- Kumar Ajith Department of Clinical Genetics, Great Ormond Street Hospital, London, UK aut NATIONALLICENCE 700 1- Walker Lisa Department of Clinical Genetics, Churchill Hospital, Old Road, Headington, Oxford, UK aut NATIONALLICENCE 700 1- Hargrave Darren Section of Paediatrics, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK aut NATIONALLICENCE 700 1- Douglas Jenny Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut NATIONALLICENCE 700 1- Stiller Charles Childhood Cancer Research Group, Department of Paediatrics, University of Oxford, Oxford, UK aut NATIONALLICENCE 700 1- Izatt Louise Department of Clinical Genetics, Guy's and St Thomas' Hospital, London, UK aut NATIONALLICENCE 700 1- Rahman Nazneen Section of Cancer Genetics, Institute of Cancer Research and Royal Marsden Hospital, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 337-342 1389-9600 10:2<337 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer